Synthetic Strategies For Drug Substances Flashcards
(6 cards)
Why do we want to use pro drugs?
- Drugs that are not sufficiently bioavailable
- Drugs that do not permeate the blood Brian’s barrier
- Drugs that have poor properties eg, solubility, taste, membrane permeability
- Drugs that have poor chemical stability
- Drugs that have poor organ or cell specificity
What are the common modifications for a prodrug?
1: Alkyl esters enhance lipophilicity (readily cleaved by ester ashes in blood, liver and other tissues, simple alkyl esters are more slowly cleaved)
2: Phosphate ester enhance water solubility (cleaved by phosphonate esterases, after cleavage drug may be very lipophilic and precipitate)
3: Carbonates and carbamates are often enzymatically more stable than simple esters
4: Amides are only used to a smaller extend (bioconversion required to a smaller extend)
5: Oximes are pro drugs of ketones, amidines and guanidines ( converted by P450 enzymes, makes drug more lipophilic)
Why is it not easy to design a prodrug?
Different species have different amounts and type so enzymes, different substrate specificities, different rates of hydrolysis.
Therefore difficult for pharmaceutical companies to generate accurate preclinical models in which to evaluate candidate pro drugs.
What are examples of prodrugs?
- Prodrugs to help improve membrane permeability
- Prodrugs to increase water solubilities
- Prodrugs to improve chemical stability
- Prodrugs to prolong in vivo activity
- Prodrugs to mask toxicity and side effects
Describe a chiral reagent
Chiral reagents are consumed in the reaction To be of practical use they must be -inexpensive -give a high ee -high chemical yields -convenient to use
What is a pro drug?
- Inactive
- usually metabolism converts it into active compound, before absorption, after absorption during absorption or at a specific site.
- Can also be activated by a non enzymatic processes such as hydrolysis
